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Background and aims: In liver cirrhosis, disruption of the intestinal barrier facilitates bacterial translocation and spontaneous bacterial peritonitis. Insulin-like growth factor I (IGF-I) is an anabolic hormone synthesised by hepatocytes that displays hepatoprotective activities and trophic effects on the intestine. The aim of this study was to investigate the effect of IGF-I on intestinal barrier function in cirrhotic rats. Methods: In rats with carbon tetrachloride induced cirrhosis, we investigated the effect of IGF-I therapy on: (a) portal pressure; (b) intestinal histology and permeability to endotoxin and bacteria; (c) intestinal expression of cyclooxygenase 2 (COX-2) and tumour necrosis factor a (TNF-a), two factors that influence in a positive and negative manner, respectively, the integrity of the intestinal barrier; (d) intestinal permeability to 3 H-mannitol in rats with bile duct ligation (BDL); and (e) transepithelial electrical resistance (TER) of polarised monolayers of rat small intestine epithelial cells. Results: IGF-I therapy reduced liver collagen expression and portal pressure in cirrhotic rats, induced improvement in intestinal histology, and caused a reduction in bacterial translocation and endotoxaemia. These changes were associated with diminished TNF-a expression and elevated COX-2 levels in the intestine. IGF-I reduced intestinal permeability in BDL rats and enhanced barrier function of the monolayers of epithelial intestinal cells where lipopolysaccharide (LPS) caused a decrease in TER that was reversed by IGF-I. This effect of IGF-I was associated with upregulation of COX-2 in LPS treated enterocytes. Conclusions: IGF-I enhances intestinal barrier function and reduces endotoxaemia and bacterial translocation in cirrhotic rats. IGF-I therapy might be useful in the prevention of spontaneous bacterial peritonitis in liver cirrhosis.

Myelodysplastic syndrome (MDS) with erythroid hypoplasia/aplasia has not yet been clearly defined, and in most patients it is mistaken for acquired pure red cell aplasia (PRCA). We report a patient with severe transfusion-dependent anemia (Hb 6.9 g/dl) and reticulocytopenia. WBC and platelet counts were normal. Bone marrow examination showed a marked trilineage dysplasia and a low percentage of erythroid precursors (3%). A diagnosis of MDS (refractory anemia according to FAB classification) with erythroid hypoplasia/aplasia was made. Repeated cytogenetic analysis of bone marrow showed normal karyotypes. Moreover, serial IgM serology and DNA analysis of the patient's sera for B19 parvovirus were negative. Other conditions known to be associated with erythroid aplasia were also absent. The patient failed hematinics and prednisone therapy. He next received r-HuEPO (200 U/kg three times weekly). This form of therapy achieved a rapid and complete erythroid response. He has remained in complete erythroid response after a 7-month period on maintenance therapy of 100 U/kg three times weekly. A review of the literature revealed only 15 well-documented cases of MDS with erythroid hypoplasia/aplasia. All had morphological evidence of myelodysplasia. These patients were predominantly elderly males, all required regular packed red cell transfusions, and had an unfavorable prognosis, mainly because of a high rate of blastic transformation (frequently preceded by a myeloproliferative phase). The mechanism of erythroid hypoplasia in this subgroup of MDS remains uncertain. However, laboratory and clinical data suggest the existence of an intrinsic stem cell defect. None of the patients received hematopoietic growth factors. To our knowledge, our patient is the first case of MDS with erythroid hypoplasia where r-HuEPO was successfully attempted. The description of more cases is necessary to delineate the value of r-HuEPO therapy in this rare variant of MDS.

Before the intervention, the frequency of appropriate prescribing based on renal function was 65 %. After the intervention, this frequency was 86 % (p < 0.001). The interventions were more frequent in the emergency department (45 %). The program required 30-45 min of pharmacist time per day. The average number of patients reviewed daily was 28. This study found that a computer-based, semi-automated drug-dosage program for renal failure patients was able to reduce the number of inappropriate orders due to renal insufficiency.

SummaryThe multimeric and subunit patterns of plasma von Willebrand factor (vWF) were analyzed in eight patients with myeloproliferative syndrome (MS) in order to investigate the possible existence of heterogeneity in the “in vivo” proteolytic cleavage of the protein, previously observed in this entity. Six patients lacked large vWF multimers, five of them having normal bleeding times (BT) and clinically documented episodes of thrombotic origin, whereas one patient had long BT and bleeding symptoms. Seven patients showed a relative increase in the 176 kDa subunit fragment while the 189 kDa polypeptide was increased in only one. In addition, another patient (and prior to any therapy) showed the presence of a new fragment of approximately 95 kDa which disappeared after Busulfan therapy. The collection of blood from these patients with proteinase inhibitors did not correct the abnormalities.The infusion of DDAVP to two patients with abnormal vWF was accompanied by: the appearance of larger vWF multimers which disappeared rapidly from plasma; an increase in the relative proportion of the satellite bands of each multimer and a further increase of the 176 kDa fragment. These data point to some heterogeneity in the vWF abnormality present in MS which may be related in part to a variable degree of proteolysis of vWF occurring “in vivo” rather than “in vitro”, and which may be associated to either a thrombotic or a bleeding diathesis. They also suggest that despite the presence of abnormal, already proteolyzed vWF, DDAVP-enhanced proteolysis occurs in MS to a similar extent to what is described in normal individuals.